Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One mechanism through which the brain obtains information about the composition of the diet involves food-induced changes in the plasma amino acid pattern (principally the "plasma tryptophan ratio"), which then cause increases or decreases in brain tryptophan levels, and in the synthesis of a neurotransmitter, serotonin, which is formed from the tryptophan. A carbohydrate-rich, protein-poor meal stimulates insulin secretion; this diminishes plasma levels of the amino acids which compete with tryptophan for transport into the brain (e.g., leucine, isoleucine and valine), thus increasing tryptophan's flux across the blood-brain barrier and its brain levels. In contrast, a high-protein meal contributes so much more of these latter amino acids to the blood stream than of the relatively-scarce tryptophan that it diminishes tryptophan's entry into the brain. This article reviews evidence that the brain actually utilizes the food-induced changes in brain serotonin in order to make choices about what to eat at the next meal. It also discusses the likelihood that a disturbance in this mechanism is involved in producing the "carbohydrate-craving" that is frequently associated with obesity. (This behavior which has been studied by allowing hospitalized subjects to choose freely among isocaloric meals and snacks of varying protein/carbohydrate ratios, typically manifests itself as a propensity to consume 30 per cent or more of the total daily calorie intake in the form of sweet or starchy snacks, usually at a characteristic time of day.) D-Fenfluramine, a drug that selectively enhances serotonin-mediated neurotransmission, also selectively suppresses "carbohydrate-craving" in these subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Carbohydrate craving, obesity and brain serotonin. 352 63

Obese persons are often reported to have marked cravings for simple carbohydrate-rich foods. Because of the proposed relationships between protein/carbohydrate selection, plasma tryptophan (TRP) to large neutral amino acids (LNAA) ratios, and brain 5-hydroxytryptamine (5-HT) neurotransmission, we examined the plasma TRP/LNAA ratios in four categories of obese subjects, before and 120 min after oral glucose tolerance test (GTT). Plasma TRP/LNAA ratios were reduced in obese, non-diabetics by 18%, the same extent as for older (approximately 52 yr old) nonobese subjects. In more advanced obesity, ie obesity associated either with glucose intolerance, hyperinsulinemia or hypoinsulinemia, plasma TRP/LNAA ratios were reduced by 25%. One hundred twenty minutes after a 100 g glucose load plasma TRP/LNAA had not been normalized. Based on animal data, these results suggest there may be diminished 5-HT neurotransmission in obese diabetics. The implications of these findings for the cravings of obese for carbohydrate-rich foods is discussed.
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PMID:Evidence for diminished brain 5-hydroxytryptamine biosynthesis in obese diabetic and non-diabetic humans. 390 26

Adult obese (ob/ob) and lean mice were allowed to self-select between diets varying in level of protein and carbohydrate, or protein and fat. Obese and lean mice self-selected 29% and 26% of their energy, respectively, from protein when fed diets varying in protein and carbohydrate. Intake of protein decreased 45% in obese mice and 32% in lean mice when diets varying in level of protein and fat were fed. These reductions in protein intake were not associated with an elevation in brain serotonin (5-HT), a putative regulator of protein intake. When the tryptophan content of diets varying in protein and carbohydrate was quadrupled in an attempt to elevate brain 5-HT and thereby reduce protein intake in obese and lean mice, neither the level of brain 5-HT nor protein intake were affected. Under the conditions of these experiments we found no evidence that protein intake was inversely related to brain 5-HT levels in obese and lean mice, nor were we able to manipulate protein intake with dietary tryptophan supplementation. The reduced protein intake in obese and lean mice fed diets varying in level of protein and fat, rather than protein and carbohydrate, may result from their greater preference for a high-fat diet than for a high-carbohydrate diet.
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PMID:Protein intake regulation in adult obese (ob/ob) and lean mice: effects of nonprotein energy source and of supplemental tryptophan. 617 15

In order to test the hypothesis that serotonergic activity is abnormal in the brains of genetically obese Zucker rats, levels of serotonin (5-HT); its amino acid precursor, tryptophan (Trp), and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA) were measured in eight brain regions in groups of obese and non-obese male rats. Plasma albumin levels as well as levels of amino acids and related compounds in plasma and in a cortical sample were also determined in the same animals. While Trp was lower in several brain regions of the obese animals, the only region showing a depressed level of 5-HT in the obese group was the mesencephalon. Obese animals also had a lower amount of 5-HIAA in the diencephalon, but no other differences were significant. Both elevations and depressions were observed in cortical amino acid levels in obese animals. The level of plasma albumin was increased in the obese group. Free Trp was decreased in the plasma of obese rats while levels of other amino acids (methionine, leucine, isoleucine, valine and phenylalanine) which compete with Trp for transport across the blood-brain barrier were elevated. Thus the combination of lower plasma free Trp and increased levels of competitive amino acids appears to contribute to decreased levels of Trp in the brain of genetically obese rats.
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PMID:Brain serotonergic activity and plasma amino acid levels in genetically obese Zucker rats. 618 36

Sprague-Dawley (S-D) and Osborne-Mendel (O-M) rats were fed either a low-fat diet (5 percent corn oil) or high-fat diet (20 percent corn oil) for a six-week-period. Brainstem and duodenal levels of tryptophan, serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindole-3-acetic acid (5-HIAA) were not altered by dietary treatment in the O-M rats. On the other hand, the high-fat diet significantly decreased brainstem 5-HT levels in S-D rats. Brainstem and duodenal 5-HT levels were decreased in O-M rats as compared to S-D rats and this phenomenon is not altered by dietary treatment. It is suggested that the O-M rat may have a alteration in the 5-HT metabolic system and that such a defect may contribute to the development of obesity.
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PMID:The effect of a high-fat diet on brainstem and duodenal serotonin (5-HT) metabolism in Sprague-Dawley and Osborne-Mendel rats. 621 Feb 59

Forty patients with the Prader-Willi syndrome have been examined. The typical features begin in gestational life with poor fetal vigor and difficulties with birth and post-partum feeding. The classical features of hypotonia, small hands and feet, cryptorchidism can be identified at this time. The delayed milestones, mental retardation and obesity become more prominent later. The average height of the patients in this series who were admitted to the Clinical Study Center was 149 cm and their weight was 114 kg. The weight and height curves show that Prader-Willi individuals are consistently shorter and heavier than normal children. Tests of endocrine function showed normal glucose tolerance. Insulin secretion was increased in relation to obesity. The rise in growth hormone (hGH) after injecting insulin to induce hypoglycemia and after the infusion of arginine was comparable to other obese individuals but was low in comparison to normal weight subjects. There was no rise in growth hormone with L-dopa administration, but there was a rise in hGH with the administration of 2-deoxy-D-glucose. The hypoglycemia produced by insulin was greater in the Prader-Willi patient than in obese controls. The rise in TRH (thyrotropin-releasing hormone) following the injection of TSH (thyrotropin stimulating hormone) was greater in the Prader-Willi patients than in the obese controls. Hypogonadism was routine in this series, and the response to LRH (luteinizing releasing hormone) was absent in all tested subjects. Treatment with clomiphene for 30 to 90 days significantly increased the response to LRH in three adult individuals who had not been treated with gonadal steroids previously and who were hypogonadal. Rectal temperature declined in three of the five Prader-Willi patients during exposure to an ambient temperature of 4 degrees C, but none of the three obese controls showed a decline. Food intake averaged 5167 kcal/d when six patients were given trays containing more food than they could eat. Food intake was not reduced when tryptophan was added to the diet. Salivary secretion was reduced in the Prader-Willi patients. A number of pulmonary function tests were significantly reduced in the study patients compared to obese or normal weight controls. The anatomic findings in four autopsied patients with the Prader-Willi syndrome showed no significant differences from those of obese subjects without this syndrome. The chromosomal pattern showed a deletion or translocation at chromosome 15 in 3 of 12 patients in whom this test was performed. These findings in 40 patients with the Prader-Willi syndrome have been compared with the information contained in 159 reports published in the medical literature.
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PMID:The Prader-Willi syndrome: a study of 40 patients and a review of the literature. 633 43

We measured plasma concentrations of tryptophan (Trp) and the other large neutral amino acids (LNAA) in 6 control and 7 obese subjects before and after they consumed a low-carbohydrate "protein-sparing modified fast" (PSMF) diet; LNAA levels in control subjects were also assessed after supplemental oral Trp. Consumption of the PSMF diet by non-obese subjects, or obesity per se, caused major reductions in the ratio of the plasma Trp concentration to the summed plasma concentrations of the other LNAA (i.e., the "plasma Trp ratio"), and may thus have diminished brain serotonin synthesis. Administration of even 2 g of supplemental Trp did not elevate the plasma Trp ratio beyond the normal range observed previously in subjects consuming carbohydrate-containing meals.
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PMID:The treatment of obesity by carbohydrate deprivation suppresses plasma tryptophan and its ratio to other large neutral amino acids. 664 85

The ratio of plasma concentrations of tryptophan to the sum of neutral amino acids (valine, isoleucine, leucine, phenylalanine and tyrosine) was found to be significantly lower in formula-fed infants as compared to breast-fed infants and to newborns at birth. This tryptophan to neutral amino acids ratio in the blood is thought to control the synthesis of serotonin in the brain. Serotonin deficiency in the developing brain based on a decreased plasma tryptophan to neutral amino acids ratio may contribute to developmental obesity and/or permanent changes of mental capacity and social adaptability as observed in human subjects who had been formula-fed as compared to those who had been breast-fed in neonatal life.
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PMID:Changes of the plasma tryptophan to neutral amino acids ratio in formula-fed infants: possible effects on brain development. 668 52

Young female obese (ob/ob) and lean mice were fed a single diet containing 10 or 20% casein or were allowed to self-select from two diets containing 10 and 50, 20 and 60, or 30 and 70% casein for 3 weeks. Obese and lean mice offered a choice of two diets varying in protein-consumed 36% and 32%, respectively, of energy from protein. Although both obese and lean mice consumed more protein when allowed to self-select, each group maintained the same energy intake as observed when a single diet was fed. Because obese mice consumed more energy than lean mice, their self-selected intake of protein was 55% greater than observed in lean mice. The increased protein intake in self-selected obese mice was associated with a decreased tryptophan:large neutral amino acid ratio in their plasma. Average nitrogen retention was only slightly less in obese mice than in lean mice, but the sites of nitrogen deposition differed considerably. Obese mice retained only 35% of their nitrogen in the carcass (skeletal muscle and skeleton) while lean mice retained 58% of their nitrogen in the carcass. In summary, young obese mice allowed to self-select from two diets varying in protein and carbohydrate consumed more protein and more energy, but deposited less nitrogen in their carcasses, than lean mice. Hyperphagia in young obese mice is not directly linked to an increased demand for dietary protein.
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PMID:Protein intake regulation and nitrogen retention in young obese and lean mice. 719 28

Young female obese (ob/ob) and lean mice were allowed to self-select from two diets varying in protein and carbohydrate, protein and fat or carbohydrate and fat for 36 days. Obese and lean mice offered a choice between two diets varying in protein and carbohydrate consumed 35 and 30%, respectively, of energy from protein. When two diets varying in protein and fat were fed, both obese and lean mice initially self-selected a higher percentage of energy from protein than when diets varying in protein and carbohydrate were fed. This pattern was rapidly reversed in lean mice and more gradually reversed in obese mice. By the end of this feeding trial, obese and lean mice were self-selecting 26 and 16%, respectively, of energy from protein. When two diets varying in carbohydrate and fat were fed, young obese mice self-selected only 44 +/- 6% of energy from the high fat diet whereas lean mice self-selected 65 +/- 4% of energy from the high fat diet. The ratio of plasma tryptophan to large neutral amino acids (valine, leucine, isoleucine, phenylalanine and tyrosine) showed a strong inverse relationship to protein intake. In summary, replacement of dietary carbohydrate with fat lowered the percentage of energy self-selected as protein. Obese mice, however, continued to consume more energy and more protein than lean mice.
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PMID:Effect of dietary fat on protein intake regulation in young obese and lean mice. 721 39


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